Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans
نویسندگان
چکیده
Background—Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. Methods and Results—MBF (mL · min 1 · g ) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n 12), saline; group 2 (n 9), 3 mg/kg N-monomethyl-L-arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n 13), 10 mg/kg L-NMMA; group 4 (n 8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n 6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF ( 53%, P 0.0001 versus baseline) and CFR ( 52%, P 0.0001 versus baseline) increased in group 3, whereas they remained unchanged in group 5, which suggests that an intact cardiac innervation was required for the increase in MBF and CFR observed in group 3. Conclusions—The results of the present study suggest that maximal adenosine-induced hyperemia and CFR in humans are constrained by neurally mediated vasoconstriction, which can be relieved by systemic NOS inhibition with L-NMMA. (Circulation. 2004;110:1431-1436.)
منابع مشابه
Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal
Philipp A. Kaufmann, Ornella Rimoldi, Tomaso Gnecchi-Ruscone, Robert S. Bonser, Thomas Myocardial Blood Flow in Humans Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2004 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas,...
متن کاملLetter regarding article by Kaufmann et al, "systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans".
BACKGROUND Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers...
متن کاملInhibition of nitric oxide synthase activity improves focal cerebral damage induced by cerebral ischemia/reperfusion in normotensive rats
Introduction: Nitric oxide seems to play a dual role in ischemia/reperfusion injury. Few studies have investigated whether it exacerbates or improves brain edema. In the present study, we inhibited the activity of nitric oxide synthase by L-NAME and evaluated the cerebral infarct volume, tissue swelling and brain edema, alongside the measurement of blood flow of the ischemic region. Methods...
متن کاملContribution of Nitric Oxide Synthase (NOS) Activity in Blood-Brain Barrier Disruption and Edema after Acute Ischemia/ Reperfusion in Aortic Coarctation-Induced Hypertensive Rats
Background: Nitric oxide synthase (NOS) activity is increased during hypertension and cerebral ischemia. NOS inactivation reduces stroke-induced cerebral injuries, but little is known about its role in blood-brain barrier (BBB) disruption and cerebral edema formation during stroke in acute hypertension. Here, we investigated the role of NOS inhibition in progression of edema formation and BBB d...
متن کاملRole of Nitric Oxide and ATP-Sensitive K+ Channels in Regulation of Basal Blood Flow and Hypercapnic Vasodilatation of Cerebral Blood Vessels in Rabbit
Background: The mechanisms underlying cerebral hypercapnic vasodilatation are not fully understood. Objective: To investigate the role of nitric oxide (NO) and ATP-sensitive potassium (KATP) channels in basal blood flow regulation and hypercapnia-induced vasodilatation in rabbit cerebral blood vessels. Methods: The change in cerebral blood flow was measured by a laser Doppler flowmeter in 18 Ne...
متن کامل